Biophysical Cues and Corneal Wound Healing

摘要 角膜中失调的伤口愈合可导致角膜瘢痕和角膜混浊，从而导致角膜炎性细胞因子的丧失。 视觉敏锐度虽然角膜伤口愈合的许多要素都得到了很好的表征，但生物物理属性 的伤口空间和这些对伤口愈合至关重要的细胞活动的影响还没有被 充分调查。沿着细胞外环境中存在的可溶性信号分子，生物物理 线索正在成为决定细胞行为的关键因素。我们建议定量分析 在整个伤口愈合过程中基质形貌和顺应性的改变。我们的假设是 伤口空间中的生物物理线索在整个伤口愈合过程中改变， 角膜基质层中角膜细胞向肌成纤维细胞的转变。肌成纤维细胞，反过来， 通过主动收缩改变伤口微环境的顺应性。最终， 伤口床中的生物物理线索将激活凋亡途径，促进肌成纤维细胞的去除， 并且恢复了透明的角膜使用测量的生物物理环境的变化作为 指南，我们将制造具有相似生物物理特性（顺应性和地形）的水凝胶基质 以确定这些改变对体外肌成纤维细胞行为的细胞后果。的信息 我们所获得的关于细胞行为、基因和蛋白质改变的信息， 在伤口愈合期间靶向生物物理学线索。伤口床的属性可以直接调节， 例如角膜基质细胞的收缩成分，以改善伤口愈合结果。

ABSTRACT Dysregulated wound healing in the cornea can lead to corneal scars and corneal haze resulting in a loss of visual acuity. While many elements of corneal wound healing are well characterized, the biophysical attributes of the wound space and the impact of these on cellular activities critical to wound healing have not been adequately investigated. Along with soluble signaling molecules present in the extracellular milieu, biophysical cues are emerging as key factors in determining cell behaviors. We propose to quantitatively analyze the alterations in stromal topography and compliance throughout the wound healing process. Our hypothesis is that the biophysical cues in the wound space alter throughout wound healing and that these directly influence the transition of keratocytes to myofibroblasts in the corneal stromal layer. The myofibroblasts, in turn, would alter the compliance of the wound microenvironment through active contraction. Ultimately, the change in the biophysical cues in the wound bed would activate apoptotic pathways, promoting removal of the myofibroblasts and an optically clear cornea would return. Using the measured alterations in the biophysical environment as a guide, we will fabricate hydrogel substrates with similar biophysical properties (of compliance and topography) to determine the cellular consequences of these alterations on myofibroblast behavior in vitro. The information that we obtain about the cellular behaviors and gene and protein alterations could enable the therapeutic targeting of biophysical cues during wound healing. Attributes of the wound bed could be directly modulated, such as the contractile elements of the corneal stromal cells, to improve wound healing outcomes.